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Tolerability of oral sorafenib in pet dogs with a diagnosis of cancer

Authors Foskett A, Manley C, Naramore R, Gordon IK, Stewart BM, Khanna C

Received 22 August 2017

Accepted for publication 12 October 2017

Published 8 December 2017 Volume 2017:8 Pages 97—102

DOI https://doi.org/10.2147/VMRR.S149678

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Professor Young Lyoo


Amanda Foskett, Christina Manley, Rebecca Naramore, Ira K Gordon, Bridget M Stewart, Chand Khanna

The Oncology Service, LLC, Leesburg, VA, USA

Abstract: Sorafenib is a multi-target small molecule inhibitor of the RAF kinase family and VEGFR-2/PDGFR. The US Food and Drug Administration approved sorafenib in human patients with liver, thyroid, or renal carcinoma. The aim of this study was to help guide future pharmacokinetic (PK) studies of sorafenib in dogs with a cancer diagnosis. Client-owned dogs were eligible if they had a cytologic or histologic diagnosis of cancer. Patients were enrolled at escalating doses of sorafenib. Patients were evaluable for the study if they received at least one dose of sorafenib and presented 1 week later for a follow-up examination, blood work, and assessment of drug tolerability. The goal of this study was not to define a maximum tolerated dose as may be reasonable in conventional cytotoxic chemotherapy drugs, but rather to describe the tolerability of this drug in dogs with a cancer diagnosis, as a prequel to future sorafenib PK studies. No patients in the study had any evidence of adverse events that were attributable to sorafenib. Doses of 3 mg/kg were well tolerated and associated with a suggestion of clinical activity, supportive of future PK, and pharmacodynamic analysis. Such future studies are recommended at this dose to define the associated exposure achieved and determine a reasonable schedule for sorafenib administration.

Keywords: sorafenib, cancer, tolerability study, developmental therapeutics
 

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